P572: VENETOCLAX AND HYPOMETHYLATING AGENT COMBINATIONS FOR THE TREATMENT OF ADVANCED MYELOPROLIFERATIVE NEOPLASMS AND ACUTE MYELOID LEUKEMIA WITH EXTRAMEDULLARY DISEASE
Authors: K. Sanber, K. Ye, H.-L. Tsai, M. Newman, A. Ambinder, A. DeZern, T. Jain
Journal: HemaSphere (2022)

Background: Progression of myeloproliferative neoplasms (MPN) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN), into accelerated phase (AP) or blast phase (BP) disease is associated with poor prognosis and decreased responsiveness to intensive chemotherapy regimens that are typically used in young and fit patients with acute myeloid leukemia (AML). Although the combination of a hypomethylating agent (HMA) and venetoclax (HMA/venetoclax) is being increasingly utilized to treat patients with advanced MPN or MDS/MPN as well as AML with extramedullary disease (EMD), outcomes in these subgroups of patients is not well characterized as they were largely excluded from the pivotal VIALE-A trial. Aims: We sought to evaluate the outcomes associated with HMA/venetoclax in disease groups that were not well-represented in the pivotal phase III VIALE-A trial. Methods: We performed an IRB-approved, retrospective chart review of patients who received HMA and venetoclax (for at least 14 days) between 1/1/2016 and 5/1/2021 at Johns Hopkins University. Composite complete response included patients who attained a complete molecular response (CMR), complete cytogenetic response (CCR) or acute leukemia response-complete (ALR-C) for patients with advanced MPN or MDS/MPN based on consensus guidelines (Mascarenhas et al., 2012), as well as complete response (CR) and CR with incomplete hematologic recovery (CRi) for patients with AML and EMD based on the ELN 2017 criteria (Dohner et al., 2017). Results: The composite CR rate and median overall survival (OS) were: 42.9% and 9.7 months for the overall population (n=35), 42.9% and 10.2 months for the BP cohort (n=21), 60% and 9.0 months for the AP cohort (n=5), 33.3% and 8.1 months for the AML with EMD (n=9). A summary of patient outcomes and their mutational landscape is represented in Figure 1. Five out of 15 patients who achieved a composite CR went on to receive an allogeneic bone marrow transplant. Patients with advanced MDS/MPN had numerically higher composite CR rate (70.0% versus 31.3%; P= 0.1054) and median OS (11.9 months versus 5.1 months; P= 0.1585) compared to patients with advanced MPN. Patients with a mutation in the SRSF2 gene had a higher composite CR rate (80% versus 20%; p= 0.0082) and median OS (10.9 months versus 8.0 months; P= 0.2614) compared to those with a wild-type SRSF2 gene. On the other hand, there was a trend towards lower composite CR in AML/blast phase patients who had EMD compared to those without EMD (33% vs 67%; P=0.1414). Image:Summary/Conclusion: The composite CR rate (42.9%) and median OS (9.7 months) for the overall patient population in our study are lower than those reported in the VIALE-A trial (42.9% versus 66.4% and 9.7 months versus 14.7 months, respectively). This is not unexpected since advanced MPN and extramedullary AML are known to have a worse prognosis than de novo AML. While limited by a small sample size, our study suggests that HMA/venetoclax may be associated with more favorable outcomes in patients with advanced MDS/MPN compared to those with advanced MPN. Mutations in the SRSF2 gene may also be associated with more favorable outcomes. These findings will need to be confirmed in larger studies and their biological basis will need to be further investigated.